Accurately detecting early cancer biomarkers can dramatically improve cancer treatment and prevention. Non-coding RNAs (ncRNAs) have recently shown promise as cancer-related biomarkers that could be used in early detection and treatment of cancer. However, current methods for detection of ncRNAs are time-intensive and costly, precluding their application to quantitative ncRNA screening on a massive scale. The proposed Optically-based RNA Biosensor (ORB) system will enable quantitative high-throughput screening for ncRNA cancer related biomarkers by Amplified Reflectometric Interference Analysis (ARIA). In the ARIA system, a DNA microarray is optically coupled to a resonating laser cavity. ncRNA hybridization to complementary probes on the microarray alters the optical properties of the array, inducing a shift in the resonant frequency of the laser. Unlike fluorescence based microarray technology, where sensing is limited to the 2-8 pM range by the brilliance of the fluorophore label and the sensitivity of the optical detector, the ARIA system is capable of detecting fM sensitivities in detection of RNA hybridization to the cDNA probes. The fully developed ORB system will be capable of quantitative screening of sera samples for ncRNA biomarkers at a massively parallel scale, allowing researchers and clinicians to screen for RNA biomarkers with unprecedented efficiency at low cost.